Current views on the mechanisms responsible for the generation of antibody variability are derived principally from sequence studies of myeloma proteins and from information of the inheritance of idiotypes, the individual antigenic determinants of immunoglobulin molecules. Support for any theory depends finally on analysis of an antibody population for which markers for and sequence studies on binding and nonbinding regions are obtainable. In such a system investigation of the ontogeny of the lymphocytes secreting these antibodies (B lymphocytes) and the influence of specific antigen and thymus-derived (T) lymphocytes of this developmental process can be made. In published and preliminary experiments we have shown that the immune response to phosphorylcholine (PC) provides an appropriate model system. The anti-PC antibodies from 15 inbred mouse strains, regardless of genetic background have identical binding specificities and idiotypes in their combining sites. The research proposes to investigate the similarity of the combining sites on these antibodies in mice (and other species), the number of responding clones and their expression in the PC-immune response and the possible transference of variable regions from one heavy-chain type to another. Analysis of these parameters will depend on isoelectric focusing of isolated antibodies and their constituent heavy and light chains, amino acid sequence analysis of heavy and light chains and the use of variable region idiotypes and constant region heavy and light chain determinants. These studies should provide basic information about the generation of antibody diversity and mechanism of antibody formation. BIBLIOGRAPHIC REFERENCES: Claflin, J. L. and J. M. Davie 1975. Specific isolation and characterization of antibody directed to binding site antigenic determinants. J. Immunol. 114:70. Claflin, J. L., S. Rudikoff, M. Potter, and J. M. Davie 1975. Structural, functional, and idiotypic characteristics of a phosphorylcholine-binding IgA myeloma protein of C57Bl/6 allotype. J. Exp. Med. 141:608.